Premed · Premed · Microbiology
Lecture 26: Fungal and Parasitic Diseases
Microbiology
Learning Objectives
By the end of this lecture, students will be able to:
- Classify medically important fungi and describe the major categories of fungal infection
- Describe the pathogenesis, clinical features, and treatment of superficial, subcutaneous, and systemic mycoses
- Identify the endemic dimorphic fungi and their geographic distributions
- Classify medically important parasites into protozoa and helminths
- Describe the life cycles, clinical presentations, and treatment of major protozoal and helminthic infections
- Discuss the role of vectors in parasitic disease transmission
Lecture Content
I. Introduction to Medical Mycology
Fungi are eukaryotic organisms distinguished by cell walls containing chitin and cell membranes containing ergosterol rather than cholesterol. They exist in several morphological forms. Yeasts are unicellular, round or oval organisms that reproduce by budding, exemplified by Candida and Cryptococcus. Molds, also called filamentous fungi, are multicellular organisms that grow as hyphae (which may be septate or aseptate/pauciseptate) forming a mycelium, as seen with Aspergillus and Mucor. The dimorphic fungi possess the remarkable ability to switch between mold form in the environment at 25 degrees Celsius and yeast form within the body at 37 degrees Celsius, summarized by the mnemonic "mold in the cold, yeast in the heat." The notable exception is Coccidioides, which forms spherules rather than yeast in tissue.
Most fungal infections are opportunistic, predominantly affecting immunocompromised hosts. However, the endemic mycoses caused by dimorphic fungi can also infect immunocompetent individuals.
II. Superficial and Cutaneous Mycoses
A. Dermatophytoses (Tinea/Ringworm)
The dermatophytoses are caused by three genera of dermatophytes: Trichophyton, Microsporum, and Epidermophyton. These fungi infect only keratinized tissues, including skin, hair, and nails, and do not invade deeper structures. Clinical presentations are named according to the body site involved. Tinea capitis affects the scalp, predominantly in children, producing broken hairs and scaling. Tinea corporis involves the body and classically presents as annular, ring-shaped, scaly plaques with central clearing. Tinea cruris affects the groin region ("jock itch"). Tinea pedis involves the feet ("athlete's foot") and is the most common dermatophytosis. Tinea unguium, or onychomycosis, affects the nails, causing thickening, discoloration, and dystrophy.
Diagnosis relies on KOH preparation showing hyphae in skin scrapings, fungal culture on Sabouraud dextrose agar, or Wood lamp examination (some Microsporum species produce blue-green fluorescence). Treatment for skin infections uses topical azoles or terbinafine, while nail and hair infections require oral terbinafine or itraconazole.
B. Malassezia furfur
Malassezia furfur is a lipophilic yeast that is part of the normal skin flora. It causes tinea versicolor (pityriasis versicolor), which presents as hypo- or hyperpigmented scaly patches on the trunk. On KOH preparation, the characteristic "spaghetti and meatballs" appearance is seen, consisting of short hyphae and round yeast cells. Treatment involves topical selenium sulfide or ketoconazole shampoo.
III. Systemic Mycoses -- Opportunistic
A. Candida Species
Candida species are normal flora of the gastrointestinal tract, oral mucosa, and vaginal mucosa. C. albicans is the most common pathogenic species and is identified by its ability to form germ tubes. C. glabrata is often azole-resistant, while C. auris is a multidrug-resistant species of particular concern as a healthcare-associated pathogen with significant infection control implications.
Candida causes a spectrum of disease. Thrush presents as oral white plaques that can be scraped off to reveal an erythematous base; it occurs in immunocompromised patients, infants, and users of inhaled corticosteroids. Vulvovaginal candidiasis is common in women and predisposed by antibiotics, diabetes, and pregnancy. Esophageal candidiasis is an AIDS-defining illness presenting with dysphagia and odynophagia. Candidemia and invasive candidiasis represent serious conditions including central line-associated bloodstream infection, endophthalmitis, and hepatosplenic candidiasis.
Treatment depends on the site and species: fluconazole is effective for most C. albicans infections, echinocandins (caspofungin, micafungin) are used for invasive disease and resistant species, and amphotericin B is reserved for refractory cases.
B. Aspergillus Species
Aspergillus is a ubiquitous mold characterized microscopically by septate hyphae with acute-angle (45-degree, V-shaped) dichotomous branching. A. fumigatus is the most common pathogenic species.
Aspergillus causes three major clinical syndromes. Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity reaction occurring in asthmatics and cystic fibrosis patients, characterized by eosinophilia, elevated IgE, and bronchiectasis. Aspergilloma (fungus ball) represents colonization of a pre-existing lung cavity, such as one left by tuberculosis, and can cause hemoptysis. Invasive aspergillosis is the most devastating form, occurring in immunocompromised patients (particularly those with prolonged neutropenia or organ transplants). It is angioinvasive, causing hemorrhagic infarction of the lungs with potential dissemination to the brain, and carries high mortality.
Diagnosis employs the galactomannan antigen test (in serum or bronchoalveolar lavage), beta-D-glucan assay, CT imaging (showing characteristic halo sign or air crescent sign), culture, and biopsy. Voriconazole is the first-line treatment for invasive disease, with isavuconazole, echinocandins, and amphotericin B as alternatives.
C. Cryptococcus neoformans
Cryptococcus neoformans is an encapsulated yeast whose polysaccharide capsule (composed of glucuronoxylomannan) inhibits phagocytosis. It is found in pigeon droppings and acquired by inhalation. Cryptococcal meningitis is the most important clinical manifestation, occurring most commonly in AIDS patients with CD4 counts below 100. It presents with insidious onset of headache, fever, and altered mental status, often accompanied by dangerously elevated intracranial pressure.
Diagnosis relies on India ink staining of CSF (showing a clear halo around the yeast), cryptococcal antigen testing (CrAg) in CSF and serum using latex agglutination or lateral flow assays. Treatment follows a phased approach: induction with amphotericin B plus flucytosine, followed by consolidation and maintenance with fluconazole.
D. Mucormycosis (Zygomycosis)
Mucormycosis is caused by organisms in the genera Rhizopus, Mucor, and Lichtheimia, which are characterized microscopically by non-septate (pauciseptate) hyphae with wide-angle (90-degree) branching. Key risk factors include diabetic ketoacidosis (DKA), neutropenia, iron overload (particularly from deferoxamine use), and organ transplantation.
The most recognizable form is rhinocerebral mucormycosis, which begins in the sinuses and aggressively invades the orbit and brain. These organisms are angioinvasive, causing thrombosis and tissue necrosis, often manifesting as a black necrotic eschar on the palate or nasal turbinate. Treatment requires surgical debridement (which is essential), systemic amphotericin B, and correction of the underlying condition. Notably, voriconazole and most azoles and echinocandins are ineffective against these organisms.
E. Pneumocystis jirovecii
Pneumocystis jirovecii is an atypical fungus classified with fungi based on ribosomal RNA analysis but lacking ergosterol in its membrane, making it resistant to standard antifungal agents. Pneumocystis pneumonia (PCP) is an AIDS-defining illness occurring when CD4 counts fall below 200. It presents with bilateral diffuse ground-glass infiltrates on chest imaging, elevated LDH, dyspnea, dry cough, and hypoxia.
Diagnosis uses methenamine silver or direct fluorescent antibody staining of induced sputum or bronchoalveolar lavage fluid, supplemented by PCR. Treatment is TMP-SMX as the first-line agent, with pentamidine as an alternative, and adjunctive corticosteroids are added for severe hypoxia. Prophylaxis with TMP-SMX is indicated when CD4 counts fall below 200.
<image>A comparison chart of the major opportunistic fungal infections. Four columns for Candida, Aspergillus, Cryptococcus, and Mucor/Rhizopus. Row 1 (Morphology): Candida -- budding yeast with pseudohyphae (illustration); Aspergillus -- septate hyphae with 45-degree branching (illustration); Cryptococcus -- encapsulated yeast with India ink halo (illustration); Mucor -- non-septate (ribbon-like) hyphae with 90-degree branching (illustration). Row 2 (Key risk factors): Candida -- immunosuppression, central lines, broad-spectrum antibiotics; Aspergillus -- neutropenia, transplant; Cryptococcus -- AIDS (CD4 <100); Mucor -- DKA, neutropenia, iron overload. Row 3 (Classic presentation): Candida -- thrush, candidemia; Aspergillus -- invasive pulmonary (halo sign on CT); Cryptococcus -- meningitis (elevated ICP); Mucor -- rhinocerebral (black eschar). Row 4 (Diagnosis): Candida -- culture, beta-D-glucan; Aspergillus -- galactomannan, CT, biopsy; Cryptococcus -- CrAg, India ink; Mucor -- biopsy showing wide aseptate hyphae. Row 5 (Treatment): Candida -- fluconazole, echinocandins; Aspergillus -- voriconazole; Cryptococcus -- amphotericin B + flucytosine then fluconazole; Mucor -- amphotericin B + surgery.</image>
IV. Endemic (Dimorphic) Mycoses
The endemic mycoses are caused by dimorphic fungi with defined geographic distributions. Unlike most opportunistic fungi, they are capable of infecting immunocompetent individuals.
A. Histoplasma capsulatum
Histoplasma capsulatum is found in the Ohio and Mississippi River valleys, associated with bat and bird droppings in environments such as caves and chicken coops. Inhaled microconidia are phagocytosed by alveolar macrophages, within which the organism converts to a yeast form that survives intracellularly. Most infections are asymptomatic or mild, but the disease can present as pneumonia mimicking tuberculosis or, in immunocompromised patients, disseminated disease with hepatosplenomegaly, pancytopenia, and oral ulcers.
Diagnosis relies on urine and serum Histoplasma antigen testing, culture, and methenamine silver staining (revealing small intracellular yeasts within macrophages). Mild disease is treated with itraconazole, while severe or disseminated disease requires amphotericin B followed by itraconazole.
B. Coccidioides immitis/posadasii
Coccidioides is found in the desert soils of the southwestern United States (Arizona, California), Mexico, and Central and South America, where it causes "Valley fever." Inhaled arthroconidia convert in tissue to spherules containing endospores rather than yeast forms. Most infections are self-limited, but the disease can cause pneumonia, erythema nodosum ("desert bumps"), and disseminated disease involving skin, bone, and meninges, particularly in immunocompromised individuals and in Filipino and African American populations.
Diagnosis uses serology (complement fixation and immunodiffusion), culture (which is a biosafety hazard requiring laboratory notification), and histopathology showing spherules. Mild disease may self-resolve; moderate to severe cases are treated with fluconazole or itraconazole, and severe or disseminated disease requires amphotericin B.
C. Blastomyces dermatitidis
Blastomyces dermatitidis is found in the Great Lakes region and the Ohio and Mississippi River valleys, associated with decaying organic matter. It causes primarily pulmonary infection that can disseminate to the skin (producing verrucous or crusted lesions) and bone. Diagnosis relies on the characteristic appearance of a broad-based budding yeast on microscopy, culture, and antigen detection. Treatment is itraconazole for mild disease and amphotericin B for severe infections.
V. Protozoan Parasites
A. Plasmodium (Malaria)
Malaria is caused by five Plasmodium species with differing clinical features: P. falciparum is the most severe and can cause cerebral malaria; P. vivax is the most common globally and causes relapses from hypnozoites dormant in the liver; P. ovale also causes relapses; P. malariae causes quartan fever; and P. knowlesi is a zoonotic species from Southeast Asia. The female Anopheles mosquito serves as the vector.
The life cycle begins when sporozoites injected by the mosquito travel to the liver for schizogony. In vivax and ovale infections, some parasites become dormant hypnozoites. Merozoites then enter the bloodstream and invade red blood cells for erythrocytic schizogony, producing the cyclic fevers that coincide with RBC lysis (tertian at 48-hour intervals for falciparum, vivax, and ovale; quartan at 72-hour intervals for malariae). Gametocytes are taken up by feeding mosquitoes to complete the cycle.
Clinical features include cyclic fevers, anemia, and splenomegaly. Severe P. falciparum malaria can cause cerebral malaria, severe anemia, acute respiratory distress syndrome, renal failure, and hypoglycemia. Diagnosis relies on thick and thin blood smears (the gold standard) and rapid diagnostic tests for HRP2 antigen.
Treatment for uncomplicated P. falciparum uses artemisinin-based combination therapies (ACTs) such as artemether-lumefantrine. P. vivax is treated with chloroquine (where susceptible) plus primaquine for hypnozoites (requiring G6PD testing first). Severe malaria requires intravenous artesunate. Prevention strategies include chemoprophylaxis (atovaquone-proguanil, doxycycline, or mefloquine), insecticide-treated bed nets, and indoor residual spraying. The RTS,S/AS01 (Mosquirix) vaccine provides partial protection.
B. Toxoplasma gondii
Toxoplasma gondii is an obligate intracellular protozoan with cats as the definitive host (producing oocysts in their feces) and humans and livestock as intermediate hosts. Transmission occurs through ingestion of oocysts from cat litter or contaminated soil, consumption of undercooked meat containing tissue cysts, or vertical transplacental passage.
In immunocompetent individuals, infection is usually asymptomatic or causes mild lymphadenopathy. In AIDS patients with CD4 counts below 100, cerebral toxoplasmosis presents with multiple ring-enhancing brain lesions and encephalitis. Congenital toxoplasmosis produces the classic triad of chorioretinitis, hydrocephalus, and intracranial calcifications.
Diagnosis employs serology (IgG and IgM), imaging showing ring-enhancing lesions, and PCR of amniotic fluid for congenital cases. Treatment is pyrimethamine plus sulfadiazine plus leucovorin, with TMP-SMX used for prophylaxis when CD4 counts fall below 100.
C. Giardia lamblia (intestinalis/duodenalis)
Giardia lamblia is a flagellated protozoan transmitted by the fecal-oral route through contaminated water, earning it the nickname "camper's diarrhea." Trophozoites attach to the duodenal mucosa without invading the tissue. Symptoms include foul-smelling, watery, non-bloody diarrhea with bloating, flatulence, and steatorrhea; the infection can become chronic. Diagnosis uses stool ova and parasite examination, stool antigen testing, or PCR. Treatment is metronidazole or tinidazole, with nitazoxanide as an alternative.
D. Entamoeba histolytica
Entamoeba histolytica is transmitted by the fecal-oral route through cysts in contaminated water or food and is endemic in tropical regions. Invasive disease manifests as amoebic dysentery with bloody diarrhea and characteristic flask-shaped ulcers in the colon, or as amoebic liver abscess presenting with right upper quadrant pain, fever, and a single large abscess with "anchovy paste" contents. Diagnosis uses stool ova and parasite examination (trophozoites with ingested red blood cells are pathognomonic), stool antigen testing, serology for liver abscess, and imaging. Treatment requires metronidazole for tissue disease followed by paromomycin for luminal cyst eradication.
E. Trypanosoma and Leishmania
Trypanosoma brucei causes African sleeping sickness and is transmitted by the tsetse fly. It invades the central nervous system, causing somnolence and eventually coma. The organism evades immune responses through antigenic variation of its variant surface glycoprotein (VSG). Treatment depends on stage: suramin or pentamidine for early disease, melarsoprol or eflornithine for late CNS involvement.
Trypanosoma cruzi causes Chagas disease (American trypanosomiasis), transmitted by the reduviid (kissing) bug. Acute infection may present with the Romana sign (unilateral periorbital edema), while chronic disease causes dilated cardiomyopathy, megacolon, and megaesophagus. Treatment uses benznidazole or nifurtimox.
Leishmania species are transmitted by sandflies and cause a spectrum of disease: cutaneous leishmaniasis (skin ulcers), mucocutaneous leishmaniasis (destructive nasal and oral lesions), and visceral leishmaniasis or kala-azar (fever, hepatosplenomegaly, pancytopenia). Treatment options include amphotericin B and miltefosine.
<image>A world map showing the geographic distribution of major parasitic diseases. Color-coded regions: Malaria (tropical Africa, Southeast Asia, South America -- Anopheles mosquito icon), Chagas disease (Central and South America -- kissing bug icon), African trypanosomiasis (sub-Saharan Africa -- tsetse fly icon), Leishmaniasis (Middle East, South Asia, Africa, Americas -- sandfly icon), Schistosomiasis (Africa, South America, Southeast Asia -- snail icon). Inset panels for each parasite show: the organism morphology (Plasmodium ring forms in RBCs, Trypanosoma trypomastigotes in blood smear, Leishmania amastigotes in macrophages), the vector, and the key clinical features. A legend distinguishes protozoal from helminthic diseases.</image>
VI. Helminths
A. Nematodes (Roundworms)
The intestinal nematodes include several important pathogens. Ascaris lumbricoides is the most common helminth worldwide, acquired through fecal-oral ingestion of eggs. Larvae migrate through the lungs (causing Loeffler syndrome with cough and eosinophilia) before reaching the small intestine where adults reside; heavy infections can cause intestinal obstruction. Treatment is albendazole or mebendazole. Enterobius vermicularis (pinworm) causes perianal itching due to nocturnal egg deposition, diagnosed by the scotch tape test, and treated with albendazole or mebendazole; household contacts should be treated. Hookworms (Necator americanus and Ancylostoma duodenale) penetrate the skin (causing ground itch), transit through the lungs, and attach to the intestinal mucosa where they feed on blood, causing iron-deficiency anemia; albendazole is the treatment. Strongyloides stercoralis is unique among helminths for its autoinfection cycle, allowing it to persist for decades. Hyperinfection syndrome occurs in immunocompromised patients, particularly those receiving corticosteroids or infected with HTLV-1; ivermectin is the treatment of choice. Trichuris trichiura (whipworm) can cause rectal prolapse in heavy infections.
The tissue nematodes include Trichinella spiralis, acquired from undercooked pork, whose larvae encyst in striated muscle causing periorbital edema, myalgia, and eosinophilia. Wuchereria bancrofti and Brugia malayi cause lymphatic filariasis (elephantiasis) transmitted by mosquitoes and treated with mass drug administration of diethylcarbamazine, albendazole, and ivermectin. Onchocerca volvulus causes river blindness, transmitted by blackflies, with microfilariae damaging skin and eyes; ivermectin is the treatment. Dracunculus medinensis (Guinea worm) is near eradication, with larvae released from the skin when the host enters water.
B. Cestodes (Tapeworms)
Taenia solium, the pork tapeworm, causes two distinct clinical entities. Intestinal taeniasis results from eating undercooked pork containing cysticerci, which develop into adult worms. Neurocysticercosis, the more dangerous condition and the number one cause of acquired epilepsy worldwide, results from ingesting eggs that develop into cysticerci in the brain. Diagnosis uses CT or MRI (showing calcified cysts and ring-enhancing lesions) and serology. Treatment combines antihelminthics (albendazole and praziquantel) with corticosteroids and antiepileptics.
Taenia saginata (the beef tapeworm) causes only intestinal taeniasis without cysticercosis. Diphyllobothrium latum (the fish tapeworm) competes with the host for vitamin B12, causing megaloblastic anemia. Echinococcus granulosus causes hydatid cyst disease in the liver and lungs, with dogs as the definitive host and sheep as the intermediate host. Cysts should never be aspirated blindly because of the risk of anaphylaxis from cyst fluid spillage; treatment involves albendazole with or without careful surgical excision.
C. Trematodes (Flukes)
The Schistosoma species use freshwater snails as intermediate hosts, with cercariae penetrating human skin during water contact. S. mansoni (found in Africa and South America) causes hepatic and intestinal disease through granuloma formation around eggs deposited in the portal system, leading to periportal (Symmer's pipe-stem) fibrosis and portal hypertension. S. haematobium (found in Africa and the Middle East) causes urogenital disease with eggs deposited in the bladder wall, leading to hematuria, bladder fibrosis, and squamous cell carcinoma of the bladder. S. japonicum (found in East Asia) produces the most eggs and causes the most severe hepatic fibrosis.
Diagnosis uses stool or urine ova and parasite examination, identifying eggs by their characteristic spines (lateral for mansoni, terminal for haematobium, and a small lateral knob for japonicum), supplemented by serology. Praziquantel is the treatment for all species.
Clonorchis sinensis (the liver fluke), acquired from undercooked freshwater fish, causes biliary disease and cholangiocarcinoma. Paragonimus westermani (the lung fluke), acquired from undercooked crab or crayfish, causes hemoptysis and lung lesions mimicking tuberculosis. Both are treated with praziquantel.
<image>A three-panel helminth classification diagram. Panel A (Nematodes -- roundworms): illustrations of Ascaris (large intestinal worm with fecal-oral lifecycle), hookworm (larva penetrating skin, adult attached to intestinal mucosa causing bleeding), Strongyloides (autoinfection cycle shown with arrows), and Trichinella (encysted larvae in striated muscle fiber). Panel B (Cestodes -- tapeworms): illustration of Taenia solium adult (scolex with suckers and hooklets, proglottids) and its dual pathology -- intestinal taeniasis from eating undercooked pork versus neurocysticercosis from ingesting eggs (brain CT showing cysticerci); Echinococcus hydatid cyst in liver. Panel C (Trematodes -- flukes): Schistosoma lifecycle diagram -- adult worms in mesenteric/vesical venous plexus, eggs deposited in tissue causing granulomatous inflammation, eggs excreted in stool/urine, miracidium hatching in water, infecting snail, cercariae released, penetrating human skin during water contact. Egg morphology comparison: S. mansoni (lateral spine), S. haematobium (terminal spine), S. japonicum (small lateral knob).</image>
